Estrogen regulation of the central enzymes involved in O- and N-linked glycoprotein assembly in the developing and the adult rabbit endocervix.

During cervical differentiation in 1- to 6-month-old rabbits, a marked increase was observed in the titer of serum estradiol, the number of secretory cells in the endocervix, and the granule content of these cells. Because these secretory granules are rich in carbohydrates it seemed likely that hormones regulate glycoconjugate biosynthesis in the endocervix. To investigate this possibility, the synthesis of O- and N-linked glycoproteins was studied in cell-free preparations from endocervical epithelium. The activity of N-acetylgalactosaminyl (GalNAc) transferase, the first enzyme in the pathway for O-linked oligosaccharide chain biosynthesis, measured in microsomes prepared from the developing cervix, was increased 8-fold. Oligosaccharyltransferase, the enzyme that catalyzes the first step in the attachment of N-linked oligosaccharide chains to proteins, was measured in microsomes prepared under the same conditions as those used for GalNAc transferase. The results of two independent assay methods revealed an estrogen-dependent 10- to 15-fold increase in oligosaccharyltransferase during cervical differentiation. Consistent with these developmental effects, ovariectomy of adult rabbits resulted in reduced (P less than 0.01) titers of serum estradiol and a 2-fold reduction in the specific activity of GalNAc transferase. When animals were treated with exogenous estradiol, GalNAc transferase activity returned to estrous control levels. The antagonistic action of progesterone on GalNAc transferase activity was verified using endocervical membranes from pseudopregnant animals. Similarly, oligosaccharyltransferase activity was reduced 2- to 3-fold when estrous animals were ovariectomized or made pseudopregnant. The treatment of ovariectomized animals with estradiol resulted in the restoration of oligosaccharyltransferase to estrous control values. Collectively, these results provide the first definitive evidence that hormones can regulate the activity of the enzymes involved in the attachment of O- and N-linked oligosaccharide chains to proteins in the endocervix.

Aneurysm of a superior cerebral vein.

Among 880 specimens of cerebral dura mater with enclosed sinuses, one had a sharply delineated bulbous conformation of the distal segment of a superior cerebral vein. There was no evidence of an arteriovenous malformation. Early plaque formation was present in the inner aspect of the thick wall of the dilated segment of vein.

Intercavernous connections of the cavernous sinuses. The superior and inferior circular sinuses.

Morphological features of the intercavernous connections of the cavernous sinuses are described and illustrated by photographs of vinylite casts. Surgeons should be aware of the course, potential size, and arrangement of the channels in the dura of the hypophyseal fossa. This is particularly important in exposure of pituitary gland by the transpheniodal route.

Anatomical features of the straight sinus and its tributaries.

The authors report a variety of arrangements of the venous channels comprising the straight sinus (sinus rectus) and its connections during a continuing study of the cerebral sinuses and their tributaries. In approximately 85% of 131 specimens of dura mater with enclosed venous sinuses derived from fresh cadavers, the straight sinus was represented by a single midline tentorial channel whereas in the remaining 15%, segments of it were doubled and in a few, tripled. In addition to these aberrations in the development of the main trunk of this sinus, the venous patterns at the junctions of the inferior sagittal sinus, vein of Galen and straight sinus showed comparable developmental inconstancies. Also in no specimens were the patterns of venous channels in the leaves of the tentorium cerebelli alike. The course, size, and connections of all the tributaries of the straight sinus have been studied and consideration given to their potentials as collateral pathways in the event either the vein of Galen or the straight sinus itself were occluded.

Human monoclonal antibody BT32/A6 and a cell cycle-independent glioma-associated surface antigen.

The purpose of this study was to ascertain how various growth parameters may influence the labeling of SK-MG-1, a human glioma cell line, by BT32/A6, a human immunoglobulin M monoclonal antibody (MAb). By growing SK-MG-1 cells at different culture split ratios, significant trends in cell growth rate, culture viability, and cell cycle state were produced. Labeling of SK-MG-1 cells by BT32/A6, however, was shown to be unaffected by culture split ratio (p > 0.05) and is therefore independent of cell growth rate, culture viability, and cell cycle state. Using flow cytometry and fluorescence-activated cell sorting, BT32/A6 was shown to label a cell surface antigen on viable, clonogenic cells of SK-MG-1. Approximately 100% of SK-MG-1 cells were shown by flow cytometry to express the BT32/A6 antigen. The recognition of a glioma-associated, cell cycle-independent surface antigen by MAb BT32/A6 makes it a promising candidate for further studies aimed at elucidating its usefulness as an adjunct in the treatment of human malignant gliomas.

Rapid imaging of human melanoma xenografts using an scFv fragment of the human monoclonal antibody H11 labelled with 111In.

H11 is a human IgM monoclonal antibody which recognizes a novel tumour-associated antigen expressed on melanoma, glioma, breast cancer, colon cancer, prostate cancer, lung cancer and B-cell lymphoma. In this study, a recombinant single-chain Fv (scFv) fragment of H11 labelled with 111In was investigated for tumour imaging in athymic mice implanted subcutaneously with A-375 human melanoma xenografts. H11 scFv was derivatized with diethylenetriaminepentaacetic acid (DTPA) for labelling with 111In. The immunoreactivity of DTPA-H11 scFv against A-375 cells in vitro ranged from 23% to 36%. 111In-DTPA-H11 scFv was rapidly eliminated from the blood and most normal tissues (except the kidneys) reaching maximum tumour/blood ratios of 12:1 at 48 h post-injection. Tumours were imaged as early as 40 min after injection. The kidneys accumulated the highest concentration of radioactivity (up to 185% injected dose/g). Tumour uptake was 1-3% injected dose/g. The whole-body radiation absorbed dose predicted for administration of 185 MBq of 111In-DTPA-H11 scFv to humans was 37 mSv. The radiation absorbed dose estimates for the kidneys, spleen and intestines were 405 mSv, 698 mSv and 412 mSv, respectively. The results of this preclinical study and a concurrent phase I trial suggest a promising role for H11 scFv for tumour imaging.

Venous channels in the tentorium cerebelli: surgical significance.

A practical surgical approach for exposure of the rostral part of the cerebellum is by way of an occipital craniectomy and incision through a leaf of the tentorium cerebelli. Venous channels of variable dimensions course in this intracranial dural process or partition. Neurosurgeons should be aware of their presence.

Venous lakes in the suboccipital dura mater and falx cerebelli of infants: surgical significance.

At birth, 25% of infants have relatively large venous channels coursing in the mid-line of the suboccipital dura mater. They connect the confluence of sinuses with the marginal sinuses. These are limited to the midline suboccipital dura mater in some, whereas in others they implicate the contiguous falx cerebelli as well. These fetal channels gradually shrink, dwindle, or otherwise disappear, and are absent in adolescents and adults. When performing a bilateral suboccipital craniectomy on an infant, one usually divides these venous channels. This may present technical difficulties. Vinylite casts have been made of a series of occipital sinuses. These demonstrated the size, variations, course, and connections of the occipital sinuses and these venous pathways.

The psychopathology of nostalgia.

Nostalgia is distinguished from depression, of which it was originally considered a variant. It is described as a pleasurable affect involving warm memories of the past. For nostalgia to be normal, it must contain a depressive component that is related to the recognition that the past is irrevocable. In its pathological form, the mood contains only the elated aspects without the acceptance of loss, or what could be described as bittersweet sentiment. The pathological form serves mainly denial and functions like a screen affect. I have attempted to show how particular developments play a role in pathological nostalgia, namely, screen affects, ego ideal formation, and rescue and family romance fantasies. The patients that were described enlisted their nostalgic pursuits as a way of remaining close to the past. These pursuits served both a defensive function, as a way of avoiding the humiliation of oedipal and later defeats, as well as offering them instinctual gratification through fantasy.